16 research outputs found

    GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region

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    The RET tyrosine kinase receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF) are critical regulators of renal and neural development. It has been demonstrated that RET activates a variety of downstream signaling cascades, including the RAS/mitogen-activated protein kinase and phosphatidylinositol-3-kinase(PI3-K)/AKT pathways. However, nuclear targets specific to RET-triggered signaling still remain elusive. We have previously identified a novel zinc finger protein, GZF1, whose expression is induced during GDNF/RET signaling and may play a role in renal branching morphogenesis. Here, we report the DNA binding property of GZF1 and its potential target gene. Using the cyclic amplification and selection of targets technique, the consensus DNA sequence to which GZF1 binds was determined. This sequence was found in the 5′ regulatory region of the HOXA10 gene. Electrophoretic mobility shift assay revealed that GZF1 specifically binds to the determined consensus sequence and suppresses transcription of the luciferase gene from the HOXA10 gene regulatory element. These findings thus suggest that GZF1 may regulate the spatial and temporal expression of the HOXA10 gene which plays a role in morphogenesis

    Modeling of Hydrogen Jet Diffusion Flames (On the Direct Influence of Molecular Viscoty

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    It was believed that the increase of molecular viscosity due to high temperature raises the dissipation rate of turbulence in low-turbulent regions in a combustion field. Hence, the objective of the present study was to verify this both experimentally and theoretically. Experiments were carried out on jet diffusion flames of hydrogen, and then, a numerical simulation was conducted for the experimental results. In the simulation, the κ-ε two-equation model was used as a turbulence model and a new source term was added to the κ-equation to represent the dissipation rate of turbulence kinetic energy due to molecular viscosity. The calculated results agree well with the experimental ones. It was found that the new source term suppresses turbulence in low turbulent regions situated around the nozzle exit and the periphery of jets, and changes the condition in the whole combustion field greatly. The present work suggested that consideration of the viscous effect is important in the modeling of turbulent combustion fields.・rights:日本機械学会・rights:本文データは学協会の許諾に基づきCiNiiから複製したものである・relation:isVersionOf:http://ci.nii.ac.jp/naid/110002494156

    Retrospective cohort study of rough-surface titanium implants with at least 25 years’ function

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    Abstract Background The longitudinal clinical outcomes over decades contribute to know potential factors leading to implant failure or complications and help in the decision of treatment alternatives. Methods The cases of all patients who received dental implants treated with titanium plasma-sprayed surfaces and whose prostheses were set in the period 1984–1990 at seven private practices were retrospectively analyzed. The cumulative survival rate, the cumulative incidence of peri-implantitis, and the complication-free prosthesis rate were calculated with Kaplan-Meier survival curves, and the factors’ influence on implant survival rate and the incidence of peri-implantitis were determined by a single factor in univariate analyses and multivariate analyses. Results A total of 223 implants and 106 prostheses were applied to 92 patients, and approx. 62% of the implants and patients dropped out over the 25 years following their treatment. The cumulative survival rates of the implants at 10, 15, and 25 years were 97.4, 95.4, and 89.8%, respectively. A significant difference was observed in the implant position. The cumulative incidences of peri-implantitis at 10, 15, and 25 years were 15.3, 21.0, and 27.9%, respectively. Significant differences were observed in the gender, implant type, and width of keratinized mucosa around the implant. The cumulative survival rates of mechanical complication-free prostheses at 10, 15, and 25 years were 74.9, 68.8, and 56.4%, respectively. The difference in the type of prosthesis resulted in significant differences. Conclusions The high rate of dropout during follow-up indicates the difficulty of determining long-term (> 25 years) prognoses. The gender, location, and width of keratinized mucosa affected the development of peri-implantitis, resulting in late failures. Implant-supported overdentures were frequently repaired. Tooth implant-supported prostheses are not recommended for long-term survival

    that binds to the HOXA10

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    doi:10.1093/nar/gki734 GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional represso

    A serine protease inhibitor camostat mesilate prevents podocyte apoptosis and attenuates podocyte injury in metabolic syndrome model rats

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    Metabolic syndrome (MetS) is associated with chronic kidney disease and proteinuria. Previously, we reported that a synthetic serine protease inhibitor, camostat mesilate (CM), mitigated hypertension and proteinuria in rodent disease models. The present study evaluated the anti-hypertensive and anti-proteinuric effects of CM in MetS model rats (SHR/ND mcr-cp). Rats were divided into normal salt-fed (NS), high salt-fed (HS), HS and CM-treated (CM), and HS and hydralazine-treated (Hyd) groups. Rats were sacrificed after four weeks of treatment. Severe hypertension and proteinuria were observed in the HS group. Although CM and Hyd equally alleviated hypertension, CM suppressed proteinuria and glomerular sclerosis more efficiently than Hyd. The HS group revealed a decrease in podocyte number and podocyte-specific molecules, together with an increase in glomerular apoptotic cells and apoptosis-related proteins in the kidney. These changes were significantly attenuated by CM, but not by Hyd. Furthermore, CM ameliorated the apoptotic signals in murine cultured podocytes stimulated with the high glucose and aldosterone medium. In conclusion, CM could exert renoprotective effects in MetS model rats, together with the inhibition of podocyte apoptosis. Our study suggests that serine protease inhibition may become a new therapeutic strategy against MetS-related hypertension and renal injuries
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